Method and apparatus to control drug therapy dosages in an implantable pump

ABSTRACT

An implantable drug infusion pump for delivering drug therapy to a patient and which also permits a patient to deliver or self-administer an additional bolus, reduces the likelihood of over dosage or under dosage by drug dosage characteristic limitations programmed into a microprocessor memory. The dose limits define the maximum and minimum amount of drug to be delivered per unit time or otherwise, reducing the likelihood that a patient may inadvertently or deliberately interfere with a treatment regimen.

This application is a divisional of U.S. application Ser. No. 09/804,136filed Mar. 12, 2001, now U.S. Pat. No. 6,796,956, which is acontinuation-in-part of U.S. application Ser. No. 09/303,307 filed Apr.30, 1999, now abandoned, the entire disclosures of which are herebyincorporated by reference.

FIELD OF THE INVENTION

This invention relates to implantable drug infusion pumps. Inparticular, this invention relates to a method and apparatus forcontrolling drug dosages that can be delivered by an implantable druginfusion pump.

BACKGROUND OF THE INVENTION

Implanted infusion pumps deliver therapeutic drugs to a patientaccording to a computer program executed by a processor that isprogrammed with drug dosing parameters. A microprocessor controls asmall, positive displacement pump according to programming instructionsdelivered to the microprocessor through an RF programming link so as topermit the implantable pump to be remotely programmed and operated. Inthe course of executing its program, the processor controls a mechanicalpump according to programmed dosage parameters.

A problem with prior art drug infusion pumps are that they runopen-loop, i.e. there is no feedback mechanism controlling drug dosing.Moreover when used for treating many disorders, implantable infusionpumps need to permit the patient to self-administer a bolus ofmedication on demand. For example, many diabetics need to administer abolus of insulin either just prior to or just after a meal. The changingof drug infusion rates is important as the insulin requirements ofdiabetic patients' change during the course of a day. Therefore, it isimportant that any drug treatment system be able to accommodate apredetermined constant delivery rate as well as any adjustments that maybe required during the course of a day. However, this frequent changingof dosage rates can lead to potential underdosing or overdosingsituations.

While prior art implantable and programmable infusion pumps permit apatient to administer additional drug dosages on demand, these prior artdevices do not adequately control the amount of patient-administereddosages increasing the likelihood that a patient may overdose orunderdose himself, adversely affecting the patient'sphysician-prescribed therapy.

A remotely programmable and implantable tissue stimulator is disclosedin U.S. Pat. No. 5,443,486 to Hrdicka et al., for a “Method andApparatus to Limit Control of Perimeters of Electrical TissueStimulators.” While the '486 Patent discloses a remotely programmabletissue stimulator and permits the patient to control the administrationof tissue stimuli, the device disclosed in the '486 patent does notprovide for programmable drug infusion therapy. Nor does the '486provide for software-based drug infusion limits.

Programmable infusion limits in implantable infusion pumps might lessenthe likelihood that a patient will overdose or underdose himself.Moreover, a software-defined limit might also lessen the likelihood thatcertain drug regimens will be used improperly—even by health-careproviders. By using a software-defined drug dosage limit, pumpmanufacturers might specify certain maximum and minimum dosages forcertain disorders by pre-programming their own infusion pumps with thedrug dosage limitations.

In order to lessen or prevent inadvertent infused drug overdoses orunderdoses, implanted drug infusion pumps require limits to be placedupon the drug delivery amount and/or frequency by health careprofessionals. An internal limit on the amount by which a patient canself-dose a drug, would be an improvement over the prior art implantableinfusion pumps. Similar limits might prevent health care providers frominadvertently overdosing, or even underdosing treatments.

SUMMARY OF THE INVENTION

A fully implantable drug infusion pump, which includes an RF programminglink, an implantable drug reservoir wherein a therapeutic drug is storedand a small, microprocessor-controlled positive displacement pump isentirely software controlled using an embedded and implantablemicroprocessor and power supply. Programming instructions and datadelivered to the microprocessor through an RF programming link are usedto limit infused drug dosage. The dosage limit data is stored inprogrammable memory within the microprocessor or in separate memorydevices. The microprocessor controlling drug administration compares theamount of drug administered over time according to the data parametersdefining the treatment regimen's dosage limits.

In the preferred embodiment of the invention, the programmable infusionpump also permits the patient to self-administer additional doses ondemand. The patient-requested additional dosage limits are specified bythe patient's health care provider and these limits can be programmedinto the implantable pump by the health care provider using the RFprogramming link. Thereafter, access to the dosage limits is notavailable to the patient. RF programming, data encryption or othersecurity software could limit access to the drug dosage limit data.Within the therapy program limits, patients would have the flexibilityto adjust the delivery of dosages to account for meals or needed bolusflow rates during the course of the day. These changes to the base flowwould be tracked by a therapy program and compared to the dosage limits.Patient notification, for example through an alarm, may be utilized ifthe actual dosage would fall above or below the programmed dosagelimits. Patient-controlled drug dosage is limited by the health careprovider-specified limit value.

In another embodiment, drug manufacturers, as well as health-careproviders, might offer implantable infusion pumps for use with certaindrugs that have precise treatment regimens. Over-dosing or under-dosingmight be precluded by way of dosing definitions programmed into securedata storage locations.

In yet another embodiment, underdosage by the patient could be avoidedif the pump is programmed to a minimum dosage or by warning the patient.The warning could be an audio alarm from the pump or an indicator on thepatient's controller to which the patient could respond by increasingthe dosage.

The same underdosage alarm could be implemented to alert the patient ofa requested overdosage, thereby alerting the patient when a dosagerequest amounts to an overdosage not allowed by the pump.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 discloses a simplified block diagram of an implantable, softwarecontrolled infusion pump providing software dosage limits.

FIG. 2 shows a full system implementation of a pump including, the pump,a catheter, two external controllers, one patient use and one medicalperson use.

FIG. 3 shows a diagrammatic view illustrating a patient controller and aphysician programmer and their communication with an implantable drugpump.

FIG. 4 illustrates a method of decreasing drug use in accordance with anembodiment of the invention.

FIG. 5 illustrates a method of preventing drug underdosage in accordancewith an embodiment of the invention.

FIG. 6 illustrates a method of reducing the number of episodes requiringdose activations in accordance with an embodiment of the invention.

FIG. 7 illustrates a method of preventing a drug overdose in accordancewith an embodiment of the invention.

FIG. 1 shows a simplified block diagram of the functional elements of animplantable and programmable drug infusion pump 100 havingre-programmable (i.e. software-specified) dosage limits. The functionalelements of the infusion pump 100 shown in FIG. 1 are small, such thatthe pump can be readily implanted into the abdomen of a patient forpurposes of controlling chronic diseases, such as diabetes. An implantedinfusion pump might also be used for acute treatment regimens, e.g. toadminister chemotherapy drugs or morphine to treat cancer or treat painrespectively.

Referring to FIG. 1, a reservoir 102 contains some appropriate volume ofdrug to be administered to the patient by a pump 104, preferably aprecision positive displacement pump drawing drug material from thereservoir 102. While FIG. 1 shows only a single reservoir and a singlepump, the invention disclosed herein is readily adapted for use withmultiple reservoirs for administering several different drugs or forincreasing the volume of a single drug that might be implanted into thepatient. Multiple pumps might be also used with multiple reservoirs toadministering different drugs at different rates and times. Multiplepumps might be used with a single reservoir for increased reliability.

The pump 104 is operatively coupled to and responsive to electricalsignals delivered to it from a control unit 106. Electrical signals fromthe control unit 106 would, for example, start and stop the pump 104 andincluding its delivery rate so as to modulate the delivery of drugs fromthe reservoir 102 to the patient. The control circuitry within thecontrol unit 106 would typically include appropriate electronic drivecircuits, the essential function of which is to couple a centralprocessor 108 to the pump 104 through appropriate interface circuitrywell know to those skilled in the art. Alternate embodiments of theinvention would of course include implementing any required pump/CPUinterface directly into the microprocessor, or selecting and/ordesigning the pump 104 to eliminate the need for an interface between itand the low power circuits of the microprocessor. Many commercial grademicroprocessors include a plethora of ancillary circuitry on a singlesubstrate including analog-to-digital converters, digital-to-analogconverters, counters, timers, clocks and so forth.

The central processor unit 108 controls the amount of drug treatmentadministered to the patient according to the therapy programinstructions stored in a program memory 110. The program memory, whichcould be resident on the same semiconductor substrate as the CPU,typically requires the ability to temporarily store and retrieve data.Random access memory 112 shown in FIG. 1 and well known to those skilledin the art, is available for use by the program executed by the CPU 108.

Those skilled in the art will recognize that while the program executedby the CPU 108 might be most economically implement in read-only-memory(ROM) structure equivalent to the ROM could include electricallyprogrammable read only memory (EPROM) 114 as well as electricallyerasable programmable read-only memory (EEPROM) 116. Both of thesealternate structures are capable of retaining executable instructionsrequired by the central processing unit 108 to operate and control thepump 100.

The EPROM 114 and the EEPROM 116 are re-programmable semi-conductormemories as those skilled in the art will recognize. EEPROM 116 isparticularly useful in the invention as it readily lends itself as arepository for drug therapy dosage characteristics and is safer than RAM(random access memory) because RAM is volatile and susceptible to errorscaused by power source interruption. EEPROM retains data for longperiods of time yet is readily re-programmed by the CPU. Manycommercially available microprocessors include addressable EEPROMdirectly on the substrate comprising the CPU further simplifying theimplementation of a software-limited dosage implantable drug infusiondevice. FIG. 2 shows the pump system embodiment including a druginfusion pump 200 and a drug infusion catheter 204, suitable to deliverdrugs to a distal sight in the body. Two external controllers are shown,one for patient use 210 and one for medical person use 220. The pump 200with the connected catheter 204 is implanted in the patient's body 216under the skin 214. For remote programming purposes, RF energy 212 flowsbi-directionally between the pump 200 and the patient use externalcontroller 210. Similarly, the health care provider uses an externalcontroller 220 to independently program the implanted pump to the desireinfusion parameters as is commonly done in the art. The manufacturer ofthe controller 220 sets the range of controller 220. A piezoelectrictransducer or other suitable audio enunciator 202 on the pump body orotherwise electrically coupled to the pump and its internal controllermight be used to provide an audible alarm to the patient in the case ofunder or overdosing.

A health care provider programs the implantable infusion pump 100 usinga remote programming device 210, such as the programming devicedisclosed in U.S. Pat. Nos. 5,443,486 and 4,676,248, “Circuit forControlling a Receiver in an Implanted Device” by Berntson. The programexecuted by the CPU 108 regularly scans the RF link (embodied by theprogramming control 120 and the uplink telemetry 122) for commands.Alternate embodiments would of course include RF communication linkcircuits that assert an interrupt control line on so-equippedprocessors. At least one command recognizable by the CPU 108 is apatient-initiated request to the pump 100 to administer a bolus of drugfrom the reservoir 102. Such a request would be sent to the pump 100 bythe patient being provided with a transponder specifically designed totransmit a bolus-request command. The functionality of thepatient-operated device 210 is limited and incapable of altering keydata programmed by a health care provider.

Both the health-care provided instructions and the patient requesteddoses are delivered to the CPU 108 through an input port on the CPU.Such an input port of the CPU 108 would include a memory mappedinput/output device or other parallel or appropriate buffered serialinput port, all of which are commonly found on many commerciallyavailable micro controllers.

In the course of programming, the infusion pump, the health careprofessional can specify a dose infusion characteristic parameter to bestored into one or more of the memory locations 124, 126 and 128 of thememory device 109 depicting FIG. 1. The dose infusion characteristicstored in memory may be one or more bytes of data (recognizable by theprogram instructions) to limit the amount, frequency, or othercharacteristic(s) of a dose of the drug to be administered to thepatient by the pump 100. The dose infusion characteristics could alsoprescribe dosage minimum dosage amounts as well.

For example, the dose infusion characteristic stored in one of thememory locations (124, 126, 128) in FIG. 1 could be used by the programstored in ROM 110 to limit the number of drug bolus deliveries that apatient may initiate in a twenty-four hour period. Alternatively, thedrug dose infusion characteristic might control the volume of drug to bedelivered upon the request of the patient over a given period of time.The bolus frequency, bolus dosage size per unit time, bolus size, orother dose information might also be stored.

Similarly, a drug dose infusion characteristic might be programmed intoone of the memory locations 124, 126 and 128 as fail-safe limits toprevent overdosing or underdosing a patient by a health careprofessional. Such an upper-limit of a drug dose might be used by theprogram in ROM 110 or EPROM 114, 116 as a fail safe to prevent a healthcare professional from accidentally overdosing or underdosing thepatient. When the health care professional programs the infusion pumpvia the RF programming link.

In an alternate embodiment, the CPU 108 might scan or poll sensors (notshown) providing data on the efficacy of the treatment. Alternatedosages might be indicated by input from one or more sensors. Doselimits would still provide a means by which maximum or minimumtreatments would not be exceeded.

Those skilled in the art will recognize that the controller 108 ispreferably a programmable microcontroller or microprocessor. Suchdevices are well known in the electronics art and many include read-onlymemory, random access memory, EPROM and EEPROM on board the device. Suchdevices also routinely include a/d converters, d/a converters, counters,timers, and other circuits usable in a real time control applicationincluding an implantable infusion pump.

Altering embodiments might include combinational as well as sequentiallogic although those skilled in the art will recognize the inherentadvantages of using a microprocessor or micro controller. Still otherembodiments would contemplate using analog devices, such as an analogcomputer to control the pump 104 in response to bodily conditions.

Program instructions for the controller 108 are stored an appropriatememory device. Program instructions might also be stored in ROM, RAM,EPROM or EEPROM as set forth above. Infusion limits or dosecharacteristics are preferably stored in a programmable memory location,such as EPROM or EEPROM because of their ability to retain data overlong periods of time, even if power is lost. In the case of randomaccess memory (RAM) power may have to be continuously applied to thememory device and any ancillary circuitry to avoid data loss.

In operation, a health care professional would preferably downloadprogramming and/or data into the memory device 109 through the RFinterlink circuitry 120 and 122. As shown in FIG. 1, these programminginstructions and/or data have passed through the central processing unit108. Depiction of this data path in FIG. 1 should not be construed aslimiting. Sufficient intelligence might be built into the RF linkcircuitry to directly load random access memory or other memory devices109 directly through the programming link.

FIG. 3 represents an alternative embodiment to the configuration of thepatient controller 310 and the physician programmer 320. In thisembodiment, the patient controller 310 contains a therapy program 306for possible drug infusion rate adjustments. The patient controller 310also contains a microprocessor 318 and memory 326 that would storetreatment information such as base rate drug flows, the maximum andminimum daily allowable doses, patient activation requests, and drugdelivery monitoring data. The health care provider would use thephysician programmer 320 to specify the drug infusion characteristicsthat may include the maximum and minimum daily allowance dosages, 24hour rolling average rate limits, nominal dosage rates, and a minimumtime interval between bolus requests. In particular, the health careprovider may program two or more different base infusion rates thatwould be acceptable in reaching the daily dosages. The nominal dosagerates would be the default rates and a patient could then select adifferent base rate using the patient controller 310 depending on theneeded amount of therapy at any given time of the day. The patientcontroller 310 through the therapy program 306 would only allow a baserate change to those rates already approved by the health careprofessional.

Optionally, the patient controller 310 may also contain a notificationmechanism to provide feedback to the patient. For example and withoutlimitation, the patient controller 310 may contain an audio speaker 302and a LCD display 304 to provide the patient with alarm, status and taskinformation. The alarm information would be generated from the changesin the patient controller therapy program output. A brief overview ofsome of the steps that the therapy program would perform in determiningwhether the proper amount of drugs are being administered are shown inFIGS. 4, 5, 6, and 7. These steps generally track drug infusioncharacteristics and allows the patient to adjust the therapy to providea more efficient and effective drug treatment.

FIG. 4 illustrates the steps that may be performed by the therapyprogram to determine whether the amount of drug being administeredshould be decreased. This may occur, for example, when the patient isnot administering any additional bolus of drug, thereby suggesting thatthe base rate could possibly be reduced. In step 402, the therapyprogram determines whether the patient has requested a dose ofmedication in a specified period of time. This dose request by thepatient could be either a bolus dose or an increase in the base rate.The specified period of time would depend on the type of drug beingadministered and may be, for example, based one or more days or one ormore hours. If the patient has requested dose activation within thespecified period of time, then the program does not make any changes, atstep 404. If, on the other hand, the patient has not requested a doseindication within the specified time, at step 406, then the drug therapycould be reduced. Either the patient would be prompted, by thenotification mechanism, to use the patient controller to select the nextlowest base rate to reduce drug usage, or the therapy program couldactivate the smallest programmed dose when the patient makes anactivation request. These steps ensure that a patient is not being overmedicated by a base infusion rate flow that is larger than the patient'scurrent medication requirements.

FIG. 5 illustrates the steps that may be performed by the therapyprogram to prevent drug underdosage. In step 502, the therapy programdetermines whether a patient is nearing an underdosage condition. Theprogram tracks the patient drug therapy and therefore, knows the actualtotal dosage being delivered to the patient. The actual total dosagedelivered to the patient is the combination of the base rate and thenumber of bolus activations over the specified time period. The programalso knows the minimum allowed dosage that is desired for a particulardrug. The program compares the actual dosage and the minimum alloweddosage. If the actual dosage is within a predetermined percentage of theminimum allowed dosage then the patient is nearing an underdosagecondition. This tracking of the total dosage allows flexibility in theadministering of the drug therapy. For example, the physician mayprescribe a base rate over the course of a period of time below theminimum dosage with the knowledge that the patient will be administeringa number of bolus dosages during that period of time. The combination ofthe base rate and the bolus dosage activations over the course of thattime period would together reach the minimum allowed dosage. If thepatient is not nearing an underdosage condition then the therapy programdoes not make any changes at step 504. If, however, the therapy programdetermines that a patient is nearing an underdosage condition then thetherapy program may prompt the patient, through the client notificationsystem, to use the patient controller to either activate a bolus dose ofmedication or to use the next highest base rate as depicted in step 506.This reminds the patient to make sure that they administer their bolusdosages. This type of notification is important, as preventingunderdosing is important in many drug therapy plans. For example, in thecase of Baclofen for spasticity, drug withdrawal has serious sideeffects and is a major concern.

FIG. 6 illustrates the steps that may be performed by the therapyprogram to determine whether the patient has requested too many bolusactivations over a specified period of time. In step 602, the therapyprogram determines whether the patient has requested more bolusactivations than allowed by the health care provider. Because theprogram tracks the patient drug therapy, the program knows the number ofbolus activations and bolus activation requests over a specified timeperiod. If the number of bolus activations is below the allowableamount, then the therapy program continues in its normal fashion at step604. If, however, the patient has had more than the allowed number ofdrug bolus activations then the patient would be prompted by thenotification mechanism to use the patient controller to select a higherbase rate in an attempt to reduce the amount of future bolus activationrequests.

FIG. 7 illustrates the steps that may be performed by the therapyprogram to prevent a drug overdosage. In step 702, it is determinedwhether the patient is currently utilizing the highest base rate allowedby the health care provider. Because the program tracks the patient drugtherapy, the program knows the current base rate and the highest baserate programmed by the physician. If the patient is not at the highestbase rate then the therapy program continues as normal at step 704.However, if the base rate is at the highest allowable setting then thetherapy program determines whether the patient is nearing his or hermaximum daily dose at step 706. If the patient is not nearing his or hermaximum daily dose then the therapy program stops the inquiry andcontinues as normal at step 708. However, if the patient is nearing themaximum daily dose then the therapy program could deny furtheractivation requests, activate the smallest programmed dose when anactivation request is made by the patient or prompt the patient toselect the next lowest base rate.

By use of the invention disclosed herein, the likelihood of overdosing apatient with a drug from an implanted and therefore an inaccessiblediffusion pump is reduced. Software based limits programmed into amicrocomputer increased the flexibility of the implanted pump for awider range of therapies compared to prior art, hard-wired devices. Thesoftware-based limits add an increased level of safety not found inprior art implantable drug infusion pumps devices.

The description of the apparatus of this invention is not intended to belimiting but is merely illustrative of the preferred embodiment of thisinvention. Those of ordinary skill in the art will recognize thatmodifications can be made without departure from the true spirit andscope of the invention.

The true spirit and scope of the inventions of this specification arebest defined by the appended claims, to be interpreted in light of theforegoing specification. Other apparatus which incorporate modificationsor changes to that which has been described herein are equally includedwithin the scope of the following claims and equivalents thereof.Therefore, to particularly point out and distinctly claim the subjectmatter regarded as the invention, the following claims conclude thisspecification.

1. A method for providing a drug therapy in an automatic drug therapydelivery system, the method comprising: (a) implanting at least oneimplantable pump into a patient; (b) programming a dose infusioncharacteristic value into a programmable memory location using a radiofrequency signal, the dose infusion characteristic value selected fromthe group consisting of a base rate drug flow, a maximum allowable dosefor a predetermined period of time, a minimum allowable dose for apredetermined period of time, a patient activation request, drugmonitoring delivery data, a rolling average rate limit for apredetermined period of time, a nominal dosage rate, and a minimum timeinterval between bolus requests; (c) delivering using the at least oneimplantable pump, in response to a patient originated stimulus, a bolusof a first drug to the patient in response to an input signal receivedby a programmable controller upon the determination of the programmablecontroller that the bolus is compliant with the dose infusioncharacteristic; (d) determining a first amount of the first drug and asecond amount of a second drug delivered to the patient; (e) determiningwhether there exists a risk of overdosage or underdosage of the drugtherapy; (f) if a risk of overdosage or underdosage is determined,notifying the patient; (g) sensing an efficacy of a treatment based onthe first drug and the second drug; and (h) determining a firstalternative dosage of the first drug and a second alternative dosage ofthe second drug from the sensed efficacy.
 2. The method of claim 1wherein the dose infusion characteristic limits the drug bolusfrequency.
 3. The method of claim 1 wherein the dose infusioncharacteristic limits the drug bolus size.
 4. The method of claim 1wherein the dose infusion characteristic limits the drug bolus frequencyand size.
 5. The method of claim 1 wherein the dose infusioncharacteristic is programmed into the programmable controller by apatient care provider.
 6. The method of claim 1 wherein the programmablecontroller is programmable using a radio frequency programming link. 7.The method of claim 1, further comprising: sensing efficacy of thebolus.
 8. The method of claim 1, wherein the alternative dosage islimited by a dose limit.
 9. A method of providing controlled treatmenttherapy to a patient using at least one implantable pump, comprising:(a) implanting at least one implantable pump into a patient; (b)receiving from a health care provider a set of drug dosage limitinformation for a first drug and a second drug describing at least onedrug therapy dosage limit, the at least one drug therapy limit selectedfrom the group consisting of a base rate drug flow, a maximum allowabledose for a predetermined period of time, a minimum allowable dose for apredetermined period of time, a patient activation request, drugmonitoring delivery data, a rolling average rate limit for apredetermined period of time, a nominal dosage rate, and a minimum timeinterval between bolus requests; (c) receiving from the patient drugdelivery instructions describing a first amount for a first drug and asecond amount for a second drug to be delivered; (d) storing in memoryhistorical information relating to the first and second amountsdelivered to the patient; (e) sensing an efficacy of the first andsecond drugs delivered to the patient based on the historicalinformation; and (f) separately administering the first drug and thesecond drug based on the sensed efficacy using the at least oneimplantable pump.
 10. The method of claim 9, further comprising:displaying feedback in the form of a notification mechanism if the drugdelivery approaches the drug therapy dosage limit.
 11. The method ofproviding a controlled treatment therapy of claim 10, wherein thenotification mechanism is a LCD display.
 12. The method of providing acontrolled treatment therapy of claim 10, wherein the notificationmechanism is an enunciator.
 13. The method of providing a controlledtreatment therapy of claim 9, wherein the drug dosage limit informationis selected from the group consisting of maximum daily dosage, minimumdaily dosage, and bolus dosage.
 14. The method of claim 9, furthercomprising: determining an alternate dosage based on the sensedefficacy, the alternate dosage limited by a dose limit.
 15. An apparatusthat is implantable into a patient and that provides a drug therapy, theapparatus comprising: a processor; a memory having stored thereinmachine executable instructions, that when executed, cause the apparatusto: sense an efficacy of a treatment, wherein the treatment incorporatesa first drug and a second drug; and separately administer within thepatient the first drug and the second drug based on the sensed efficacyand a dose infusion characteristic value selected from the groupconsisting of a base rate drug flow, a maximum allowable dose for apredetermined period of time, a minimum allowable dose for apredetermined period of time, a patient activation request, drugmonitoring delivery data, a rolling average rate limit for apredetermined period of time, a nominal dosage rate, and a minimum timeinterval between bolus requests using at least one implantable pump. 16.The apparatus of claim 15, wherein the instructions further cause theapparatus to: administer the first drug and the second drug at differentrates and different times.